Whole body oxygen consumption is generally a reflection of metabolic needs since oxygen supply is in great excess of oxygen consumption or uptake at rest. In the presence of hypoxia, oxygen uptake often falls below basal levels and may be limited by the depressed oxygen supply. This is particularly important for the newborn and infant in whom compensatory adaptation to hypoxia may be very limited. Prior studies in adults of many species have shown that changes in cardiac output, hemoglobin, and hemoglobin oxygen affinity have little effect on oxygen uptake at rest. These studies, however, were usually conducted in anesthetized normoxic adult animals and may not be applicable to the stressed young mammal with the subnormal oxygen consumption. It is the aim of this proposal to explore methods for acutely augmenting oxygen uptake that has been depressed by hypoxia due either to anemia or hypoxemia. Using the awake, unsedated lamb as a model, a steady state will be obtained under normoxic conditions and the following will be measured: oxygen consumption rate, hemoglobin concentration, cardiac output and hemoglobin oxygen affinity. The lamb will then be made hypoxic (reducing oxygen consumption) either by decreasing inspired oxygen concentration (hypoxic hypoxia) or by decreasing hemoglobin concentration (anemic hypoxia). We will then alter oxygen supply by changing cardiac output, hemoglobin, or hemoglobin oxygen affinity in the presence of hypoxic hypoxia, or hemoglobin oxygen affinity in the presence of anemic hypoxia. The efficacy of these manipulations will be judged by measuring changes in oxygen consumption. These data will additionally be able to define: 1) the mechanisms invoked by the intact and awake neonate to maintain oxygen uptake with stress; 2) the limits of this compensation; and 3) any age-related differences in the response to hypoxia. The information provided by this study should be applicable to the hypoxic human infant and allow us to develop a rational and systematic approach to aid in the management of such children.